This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Springer, K. L. Articles by Weinberg, A. Search for Related Content PubMed PubMed Citation Articles by Springer, K. L. Articles by Weinberg, A.

How Evolution of Mutations Conferring Drug Resistance Affects Viral Dynamics and Clinical Outcomes of Cytomegalovirus-Infected Hematopoietic Cell Transplant Recipients

Division of Infectious Diseases,¹ Pediatric Infectious Diseases, University of Colorado Health Sciences Center,⁴ The Children's Hospital, Denver, Colorado,³ VA Medical Center and Oregon Health Sciences University, Portland, Oregon²

Received 9 June 2004/ Returned for modification 27 August 2004/ Accepted 10 September 2004

Infection with cytomegalovirus (CMV) remains a significant cause of morbidity and mortality among hematopoietic cell transplant (HCT) recipients. We describe two pediatric HCT recipients who developed persistent and severe drug-resistant CMV infections. CMV resistance to foscarnet and ganciclovir was detected after only 6 and 11 weeks of therapy, respectively. Viral pol mutations associated with drug resistance in these patients included T838A (a novel mutation) and D588N, which were shown by marker transfer to confer foscarnet and multidrug resistance, respectively. Each of these mutations significantly reduced in vitro replication of CMV, suggesting that they may decrease viral fitness. This finding was further supported by the disappearance of mutations upon withdrawal of antiviral pressure in one patient. Novel antivirals or combination therapy may be required for the treatment of drug-resistant CMV in HCT recipients and perhaps in other severely immunocompromised patients.

This article has been cited by other articles:

• Chou, S., Marousek, G. I., Van Wechel, L. C., Li, S., Weinberg, A. (2007). Growth and Drug Resistance Phenotypes Resulting from Cytomegalovirus DNA Polymerase Region III Mutations Observed in Clinical Specimens. Antimicrob. Agents Chemother. 51: 4160-4162 [Abstract] [Full Text]  
• Scott, G. M., Weinberg, A., Rawlinson, W. D., Chou, S. (2007). Multidrug Resistance Conferred by Novel DNA Polymerase Mutations in Human Cytomegalovirus Isolates. Antimicrob. Agents Chemother. 51: 89-94 [Abstract] [Full Text]  
• Gilbert, C., Boivin, G. (2005). New Reporter Cell Line To Evaluate the Sequential Emergence of Multiple Human Cytomegalovirus Mutations during In Vitro Drug Exposure. Antimicrob. Agents Chemother. 49: 4860-4866 [Abstract] [Full Text]